The long-term objectives of the proposed research are to develop a better understanding of a) cellular functions and interactions in the ovary and b) the role ovarian somatic cells have in the maintenance and control of ovarian functions. Specifically, the functions of granulosa cells and theca cells will be examined. In addition, interactions between these two cell types which are mediated via soluble peptides will be investigated. Three specific aims are proposed: 1) to characterize appropriate markers (specific secreted proteins) of granulosa cell function and cytodifferentiation; 2) to analyze the control of granulosa cell function and cytodifferentiation; 3) to characterize factors produced by theca (i.e. stromal) cells that act on granulosa cells to regulate growth, function and cytodifferentiation. Proteins of interest will be isolated from serum-free conditioned medium obtained from primary cultures of rat granulosa cells or theca cells. These proteins will be purified by high pressure liquid chromatographic procedures and antibodies will be produced to the proteins. The influence of hormones and paracrine factors, derived from theca cells, have on the production of specific proteins secreted by granulosa cells will be used as a functional analysis. Granulosa cell cytodifferentiation will be investigated through an analysis of the effects of regulatory agents on the production of secreted and cellular proteins. The results of the proposed research will provide information on 1) the functions of granulosa cells and theca cells, 2) theca-granulosa cell interactions, 3) the hormonal control of these cellular functions and interactions, and 4) the influence of these cellular functions and interactions on the maintenance and control of oogenesis and folliculogenesis. In addition, these investigations will provide insight into general mesenchymal-epithelial cell interactions which occur in most organs such as the prostate, mammary gland, kidney and testis.